Hydrobromide

The dextrorotatory isomer of 3-methoxy-A-methylmorphinan, a synthetic morphine derivative (Roinilar hydrobromide , Tusilan ) is employed exclusively as an antitussive agent. Its levorotary isomer (in the form of the 3-hydroxy tartrate) is described next. These compounds differ from morphine chemically in lacking the -O- bridge between carbons 4 and 5, the OH group at C6, and 

Dextromethorphan hydrobromide is administered orally in doses of 10 to 20 mg one to four times daily to adults. This dose is reduced to a half for children over 4 years of age and to a quarter for children under 4 years of age. 

Trade Name Manufacturer Country Year Introduced 

Two mols, for example, 270 grams, of racemic a-methylphenethylamine base are reacted with one mol (150 grams) of d-tartaric acid, thereby forming dl-a-methylphenethylamine d-tartrate, a neutral salt. The neutral salt thus obtained is fully dissolved by the addition of sufficient, say about 1 liter, of absolute ethanol, and heating to about the boiling point. The solution is then allowed to cool to room temperature with occasional stirring to effect crystallization. The crystals are filtered off and will be found to contain a preponderance of the levo enantiomorph. 

The residual solid in the mother liquors Is repeatedly and systematically crystallized, yielding a further fraction of 1-a-methylphenethylamine d-tartrate which may be purified by recrystallization. d-a-Methylphenethylamine may be readily recovered from the mother liquors by the addition of tartaric acid thereto for the formation of acid tartrates and separation of d-a-methylphenethylamine d-bitartrate by crystallization. 

The free base of either optical isomer may be obtained by addition to the d-tartrate in the case of the levo isomer and the d-bitartrate in the case of the dextro isomer of alkali in excess, as, for example, by the addition of an aqueous solution of caustic soda, which will cause the base to separate as an oil which may be recovered and purified by any well-known procedure. The base Is exactly neutralized with sulfuric acid to give the sulfate. 

Nabenhauer, F.P. U.S. Patent 2,276,508 March 17,1942 assigned to Smith, Kline French Laboratories 

---

Anilines react with ct-haloacetophenones to give 2-arylindoles. In a typical procedure an W-phenacylaniline is heated with a tw o-fold excess of the aniline hydrobromide to 200-250°C[1]. The mechanism of the reaction was the subject of considerable investigation in the 1940s[2]. A crucial aspect of the reaction seems to be the formation of an imine of the acetophenone which can isomerize to an aldimine intermediate. This intermediate apparently undergoes cyclization more rapidly (path bl -> b2) than its precursor (Scheme 7.3). Only with very reactive rings, e.g, 3,5-dimethoxyaniline, has the alternative cydiz-ation (path al a2) to a 3-arylindole been observed and then only under modified reaction conditions[3],... 

The crystal and molecular structures of 2-amino-4-phenylthiazole hydrobromide have been determined by radiocrystallography the angle between the thiazole and phenyl rings was found to be 19 . The major features are reported in Fig. VI-4 (142). 

Fig. Vl-4. Geometry of thiazole ring in 2-arniro-4-phenylthiazole hydrobromide. Italicized values are interatomic distances (A) other numbers are angles in degrees. From Ref. 342.

Bromination of 2,4-dimethylselenazole with cold bromine gives an unstable monobrominated derivative initially (m.p. 168°C). which is easily converted to a product [m.p. 205°C (decomp.)] considered by Haginiwa to be 5-bromO-2,4-dimethylselenazole hydrobromide (19). 

Unlike nitration. 2-amino-4-methylselenazole can be directly bromi-nated, using bromine in carbon tetrachloride solution, to give 2-amino-5-bromo-4-methylselenazole hydrobromide [m.p. 180°C (decomp.)] (19). The free base cannot be isolated. Use of excess of bromine can lead to destruction of the molecule. 

Starting from 2-bromoethylamine hydrobromide and selenourea, Chu and Mautner (60) prepared the salt of 2-(aminoethyl)-selenopseudourea, which cyclizes upon heating in aqueous solution to give 2-aminoselenazoline (Scheme 58). 

Amino-A.-selenazoline and its 5-methyl derivative have previously been obtained by Baringer (61) starting from 2-bromoethylamine hydrobromide and l-amino-2-bromopropane hydrobromide, respectively, by reaction with potassium selenocyanate. 

DiaminO 4,4-dimethyl-l,3,5-thiadiazine hydrobromide was isolated as by-product (418). Benzene sulfonates of cyanohydrin prepared from sodium cyanide and an halobenzoaldehyde, when treated with thiourea or its derivatives, afford 2,4-diamino-5-(p-halogenophenyl)-thiazole benzene sulfonates (447). Similarly, cyanoamido thiocarbamates obtained from cyanamide and isothiocyanates yield substituted 2,4-diaminothiazoles (598). 

Scopolamine (42), an optically active, viscous Hquid, also isolated from Solanaceae, eg. Datura metell. decomposes on standing and is thus usually both used and stored as its hydrobromide salt. The salt is employed as a sedative or, less commonly, as a prophylactic for motion sickness. It also has some history of use ia conjunction with narcotics as it appears to enhance their analgesic effects. BiogeneticaHy, scopolamine is clearly an oxidation product of atropiae, or, more precisely, because it is optically active, of (—)-hyoscyamiae. 

---